Compositions comprising n-acetyl methyl gaba and related methods

ABSTRACT

The present invention is directed to compositions comprising N-Acetyl Methyl GABA, methods of preparing N-Acetyl Methyl GABA and compositions including N-Acetyl Methyl GABA, and methods of using N-Acetyl Methyl GABA for instance to improve sleep and control anxiety.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 63/018,185, filed Apr. 30, 2020, which is incorporatedby reference herein in its entirety.

FIELD OF THE INVENTION

The present invention relates to compositions comprising N-Acetyl MethylGABA, methods of preparing N-Acetyl Methyl GABA and preparingcompositions including N-Acetyl Methyl GABA, and methods of usingN-Acetyl Methyl GABA for instance to improve sleep and reduce anxietyand stress.

BACKGROUND

GABA (gamma-aminobutyric acid; NH₂CH₂CH₂CH₂C(O)OH) acts as aneurotransmitter in the brain, controlling anxiety and contributing tomotor control and many other functions of the cortex. GABA isproblematic as an oral drug because the polar ends (amino- (—NH₂);carboxyl- (—COOH)) of the GABA molecule hinder its transport across theblood-brain barrier. GABA receptor agonists may provide anxiolytic andstress-relieving effects, and may for instance reduce muscle spasms.

Due to stress and lifestyle, many people find it difficult to fall orstay asleep, or to feel calm. Falling asleep is a major problem in themodern world.

The use of GABA as for instance a sleep aid is limited by its relativeinability to pass the blood-brain barrier. Phenylated GABA derivativessuch as fenibut are used as a sleep aid, however, fenibut has beenbanned in some jurisdictions. Possibly, its phenol metabolites causeneurotoxicity in the brain. Kavinace® was a sleep aid that included aphenylated GABA (4-amino-3-phenylbutyric acid). However, that version ofthe sleep aid has been discontinued.

SUMMARY OF THE INVENTION

The present invention is directed to N-Acetyl Methyl GABA andcompositions thereof. The present invention is also directed to aprocess for preparing N-Acetyl Methyl GABA, comprising, consistingessentially of, or consisting of the steps of: methylating the carboxylgroup of GABA and acetylating the amino group of GABA to prepareN-Acetyl Methyl GABA; and optionally, purifying the N-Acetyl MethylGABA. In addition, the present invention is directed to methods foraiding sleep, treating insomnia, and reducing anxiety and/or reducingstress in a subject, and related methods.

In an embodiment, a composition of this invention comprises N-AcetylMethyl GABA. In an embodiment, a composition of this inventioncomprises, consists essentially of, or consists of, N-Acetyl Methyl GABAmade by a process of this invention.

In an embodiment, this invention comprises a process for preparingN-Acetyl Methyl GABA, comprising the steps of:

-   -   a. methylating the carboxyl group of GABA;    -   b. acetylating the amino group of GABA to prepare N-Acetyl        Methyl GABA; and then    -   c. optionally purifying the N-Acetyl Methyl GABA.

In an embodiment, this invention comprises methods of aiding sleepand/or treating insomnia, reducing stress and/or anxiety, and improvingqualities and symptoms identified in the Examples and throughout thisapplication.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 represents a gas chromatogram of an N-Acetyl Methyl GABAdistillate of this invention.

FIG. 2 represents an FT-IR scan of nearly 100% pure N-Acetyl Methyl GABAof this invention after purification of an N-Acetyl Methyl GABAdistillate by a high purity distillation unit.

FIG. 3 is a bar graph representing a summary of improvements in 47subjects' sleep quality, restfulness/wakefulness, mental clarity andmemory, mood, daytime energy, stress, anxiety, body aches/pains, stressheadaches, and digestive issues after administration of an N-AcetylMethyl GABA composition of this invention for a nighttime sleep period.

FIG. 4 is a bar graph representing a summary of improvements in 19subjects' stress, anxiety, mental clarity and memory, mood, daytimeenergy, and sleep quality after administration of an N-Acetyl MethylGABA composition of this invention.

DETAILED DESCRIPTION

The present invention is directed to N-Acetyl Methyl GABA andcompositions comprising, consisting essentially of, or consisting ofN-Acetyl Methyl GABA. N-Acetyl Methyl GABA has the chemical structureCH₃C(O)NHCH₂CH₂CH₂C(O)OCH₃ (Molecular Formula: C₇H₁₃O₃N. MolecularWeight: 159.183). The present invention is also directed to methods forpreparing N-Acetyl Methyl GABA, and methods for administering N-AcetylMethyl GABA and its composition to a subject.

In the brain and overall central nervous system, GABA may block GABAreceptors and reduce anxiety and stress, allowing a subject to feel morerelaxed and enjoy improved sleep, mood, mental clarity and memory,daytime energy, and other beneficial effects. In addition, by reducinganxiety and stress, GABA can decrease body aches and pains, stressheadaches, and digestive issues.

According to the present invention, without being bound by theory,N-Acetyl Methyl GABA administered to a human or other mammal istransported across the blood-brain barrier, where it may be convertedinto GABA, and reduce anxiety and stress in a subject. Also withoutbeing bound by theory, metabolites of N-Acetyl Methyl GABA include anacetate group and a methyl group, which may be used in other biochemicalreactions in the brain and/or provide effects in the brain. In anembodiment, after using N-Acetyl Methyl GABA as an overnight sleep aid,human subjects experience uninterrupted sleep and little to nogrogginess upon waking at the end of the sleep period, in contrast togrogginess upon waking for instance as is common with other sleep aids.In an embodiment, general body inflammation and aches and pains in thesubject are also reduced. In an embodiment, the subject's mind is clearand attitude is positive after sleep aided by N-Acetyl Methyl GABA.Without being bound by theory, these effects are or may be due toN-Acetyl Methyl GABA action as an anxiolytic agent.

The present invention is directed in part to a novel synthesis methodfor preparing N-Acetyl Methyl GABA comprising, consisting essentiallyof, or consisting of the steps of methylating the carboxyl end of theGABA molecule and then acetylating the amino end to prepare N-AcetylMethyl GABA, and then optionally, purifying the N-Acetyl Methyl GABA.Without being bound by theory, these modifications render GABA non-polarand able to be transported across the blood-brain barrier.

In an embodiment, the present method uses only two synthesis steps andsafe recoverable solvents, yields about 95% (highly pure) product(N-Acetyl Methyl GABA), and optionally includes a third (purification)step to increase purity of the N-Acetyl Methyl GABA. Reaction conditionsare safe and easily controlled. In an embodiment, during saidacetylation step, a neutral or basic pH (for instance about pH 6-8.5, orpH 6.5-8) is maintained, and a solvent with a lower boiling point thanN-Acetyl Methyl GABA is used. Other synthesis steps may provide lowyields of N-Acetyl Methyl GABA and/or use undesirable or dangeroussolvents, and may for instance require an extraction procedure whichdecreases yield and uses more solvent(s) than the present method.Solvent extraction would require two more steps and is messy andtime-consuming, requiring drying of the product as well. Due to solventvolatility and the low boiling point of the product, much of the productcould be lost in the drying step. Other synthesis steps also includereaction conditions that may be violent and unsafe to personnel and/orthe environment, such as the reaction of acetyl chloride with substrate.Some solvents described in the art are carcinogenic and toxic to thebody, such as DMF (dimethylformamide), methylene chloride, acetonitrile,pyridine, and are not preferred in the present invention.

In an embodiment, before the optional purifying step, N-Acetyl MethylGABA prepared according to this invention is at least 85% pure,preferably at least 90% pure, more preferably at least 95% pure; and/orafter said purifying step, said N-Acetyl Methyl GABA is at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99%, or about 100% pure.In an embodiment, the N-Acetyl Methyl GABA is 98% to 100% pure. In anembodiment, a composition of the present invention consists essentiallyof N-Acetyl Methyl GABA having the purity levels described above, andfor instance as described in FIG. 1 .

In an embodiment, before the optional purifying step, the synthesis ofN-Acetyl Methyl GABA according to this invention includes a high yieldof about 80-100% w/w according to theoretical weight; in an embodiment,a high yield of about 85-100% w/w, a high yield of about 90-100% w/w, ahigh yield of about 95-100% w/w, a high yield of about 98-100% w/w,and/or a high yield of about 100% based on theoretical weight.

The below definitions and discussion are intended to guide understandingbut are not intended to be limiting with regard to other disclosures inthis application. Throughout this application, references to percentage(%) of compositions of the present invention refers to the % by weightof a given substance to the total weight of the composition beingdiscussed, also signified by “w/w” or “wt/wt”, unless stated otherwise.

A “composition” according to the present invention comprises, consistsessentially of, or consists of, N-Acetyl Methyl GABA. A composition ofthis invention may be pure N-Acetyl Methyl GABA, for instance at least85%-100% including for instance at least 90%, 95%, 98%, 99%, or about100% pure. A composition of the present invention may be a nutraceuticalor pharmaceutical composition, formulated into nutraceutical orpharmaceutical dosage forms comprising for instance liquids, emulsions,tablets, capsules, powders, chews, gummies, transdermals, injectables,suppositories, dietary supplements, topical creams or gels, lozenges,pills, and so forth. In an embodiment, a composition of the presentinvention is in solid, liquid, or semi-liquid form, for instance asprepared in Example 1 Step 2, comprising at least 95% w/w N-AcetylMethyl GABA. In an embodiment, a composition of this invention is fororal administration to a subject, with pharmaceutically and/ornutraceutically acceptable ingredients such as discussed below. In anembodiment, N-Acetyl Methyl GABA is the active ingredient of thecomposition.

In an embodiment, without being bound by theory, a compositioncomprising N-Acetyl Methyl GABA according to this invention isadministered with an effective amount of N-Acetyl Methyl GABA to asubject, so that the N-Acetyl Methyl GABA reaches the subject'sbloodstream and tissues including brain tissue, for instance to aidsleep by improving or achieving a good to excellent period of sleep,and/or to reduce anxiety or to treat insomnia or to otherwise act on andhelp the subject as described herein. In an embodiment, N-Acetyl MethylGABA and/or its metabolites or other components reaches the subject'sbloodstream and tissues including brain tissues and other CNS tissue toact at GABA receptors to for instance reduce anxiety and/or stress inthe subject. In an embodiment, an “effective amount” of N-Acetyl MethylGABA to be administered to a human subject is about 10 mg to about 1000mg (preferably orally administered, preferably an adult human subject).In an embodiment, this amount may be higher or lower than the aboverange, for instance 1 mg to 2000 mg, for instance 200-600 mg or e.g. 300mg as discussed throughout this application. A daily dose according tothis invention may be limited by safety regulations for instance aspromulgated by a regulatory agency. In an embodiment, N-Acetyl MethylGABA is present in an amount of about 1% to about 100% (w/w) of acomposition of this invention. In an embodiment, N-Acetyl Methyl GABA ispresent in an amount of about 0.1-100% (w/w), 1-50% (w/w), 1-30% (w/w),2-20% (w/w) of a composition of this invention. In an embodiment,N-Acetyl Methyl GABA is present in an amount of about 10-20% (w/w),14-16% (w/w), or about 15% (w/w) of a composition of this invention. Inan embodiment, N-Acetyl Methyl GABA is present in an amount of about3-5% w/w of a composition of this invention. For instance, as shown inExamples 3-6, a composition of this invention may include about 300 mgN-Acetyl Methyl GABA in a serving size of about 8 g (2 liquid teaspoons)of a composition of this invention, for instance to improve mood, energylevels, sleep quality, and other parameters discussed in the Examples.In an embodiment, the composition is about 3-4% N-Acetyl Methyl GABA(w/w) (0.3 g/8 g*100%). Without being bound by theory, the N-AcetylMethyl GABA may be metabolized to GABA in the subject's body, preferablyonce past the subject's blood-brain barrier. In a non-human mammal, adose may be about the same as in a human, adjusted per kilogram ofweight of the mammal. In an embodiment, an “effective amount” ofN-Acetyl Methyl GABA to be administered to a subject, for instance toaid sleep or to reduce anxiety in a human adult subject, is a daily doseof about 200-600 mg. In an embodiment, a “daily dose” of N-Acetyl MethylGABA to be administered to an adult human subject in a method of thisinvention is about 200-600 mg, such as 200 mg or 300 mg or 400 mg orother amounts within said range such as 250 mg-400 mg N-Acetyl MethylGABA.

In an embodiment, a composition of the present invention is in the formdescribed in Example 1 Step 2 or Step 3 of this application. Acomposition of the present invention may further comprise one or moreactive ingredients to enhance sleep and/or relaxation, as well asexcipients, additives, and/or other substances. In an embodiment, acomposition of this invention is in the form of an emulsion of aliposome. In an embodiment, the liposome comprises liquid lecithin,sodium lauroyl lactylate and/or sodium stearoyl lactylate, butyleneglycol and glycerine. Without being bound by theory, liposomes enhancethe absorption of N-Acetyl Methyl GABA into the bloodstream and/or thebrain. In an embodiment, melatonin is added to the composition toenhance the effects of the composition in an embodiment in a synergisticmanner. In an embodiment, melatonin may be added to a composition ofthis invention; in an embodiment, melatonin is added in amount of about1-10 mg, for instance 5 mg, for instance as a daily dose to an adulthuman with a daily dose of N-Acetyl Methyl GABA. See for instanceExamples 3-6 for further examples of a composition of this invention. Inan embodiment, a composition of this invention includes an oil such asMCT (medium-chain triglyceride) oil, vegetable oil, coconut oil, palmoil palm kernel oil, sesame oil, soybean oil, almond oil, rapeseed oil,sunflower oil, corn oil, peanut oil, olive oil, castor oil, saffloweroil, and the like. An oil may be fractionated, for instance removinglong chain fatty acids from the oil resulting in medium chaintriglycerides (e.g. MCT oil). In an embodiment, a composition of thisinvention includes flavors including natural flavors such as orange,bitter masking agent (e.g. a maple derivative), cinnamon, and/orpeppermint, and sweeteners/stabilizers such as xylitol, mannitol,dextrose, glucose, sucrose, fructose, sorbitol, and the like, and/ornatural sweeteners such as stevia, luo han guo, and/or glycerine. In anembodiment, a composition of this invention includes preservatives suchas glycerine, potassium sorbate, and/or vitamin E. In an embodiment, anatural coloring agent is included in a composition of this invention,such as curcumin. In an embodiment, a thickener and stabilizer such asguar gum may be added to a composition of this invention. In anembodiment, an ingredient added to a composition of this invention mayserve more than one function, or may serve only 1 specified function.

In an embodiment, a composition of this invention comprises (w/w) about3-5% N-Acetyl Methyl GABA; 55-75% water; 10-20% preservatives such asglycerine, potassium sorbate and/or vitamin E oil; 4-8% oil such as MCToil; 5-10% lecithin or suitable substitute; 2-10% flavoring and/orsweetening agent such as orange flavor, xylitol, stevia extract (e.g.90%), bitter mask powder, luo han guo (e.g. 50%), peppermint oil, and/orcinnamon; 0.1-3% thickener/stabilizer including for instance guar gum;and optionally 0.1-10% w/w additional agents such as melatonin(typically about 0.05-0.1% w/w).

In an embodiment, combining a suitable solvent combination such aswater, glycerine, butylene glycol with the liquid lecithin and asuitable surfactant such as sodium lauroyl lactylate, sodium stearoyllactylate or Tween 60 makes the lecithin form hollow spheres whichencloses the active ingredients: N-Acetyl Methyl GABA and optionallyMelatonin. Without being bound by theory, these spheres form by liningup the phosphorus moiety of the lecithin on the outside of the sphereand the lipid end on the inside of the sphere. These spheres are carriedinto the body and blood stream where they combine with cell membranes torelease the active ingredients inside the cell. In an embodiment,liposomes, liposome emulsions, and other delivery methods for N-AcetylMethyl GABA are prepared according to methods known in the art.

In an embodiment, a composition of this invention is in the form of acapsule for instance composed of gelatin or cellulose such as a softgelor hard gel capsule. As the N-Acetyl Methyl GABA has a solvent-likenature, to place it in a soft gel or hard gel, it is preferablyformulated with a surfactant to thicken and smooth out the viscosity. Inan embodiment, 30-75% (w/w) sodium lauroyl lactylate or sodium stearoyllactylate is mixed with 25-70% (w/w) N-Acetyl Methyl GABA to make aclear liquid that is more viscous than N-Acetyl Methyl GABA alone. Otheroils or surfactants may be used with this combination or with N-AcetylMethyl GABA alone. Vitamin E oil (for instance 1-10% (w/w) of thecomposition) may be mixed with N-Acetyl Methyl GABA. Other oils such assafflower oil, sunflower oil, soy oil, jojoba oil, other vegetable oils,may be used at applicable levels for instance with the sodium lauroyllactylate. Other lactylates may be used, such as sodium stearoyllactylate. In an embodiment, compositions of this invention may beprepared according to methods generally known in the art. In anembodiment, 400 mg N-Acetyl Methyl GABA may be placed with 400 mg sodiumlauroyl lactylate or sodium stearoyl lactylate and filled into an 800 mgsoft gelatin capsule using a capsule manufacturing machine.

In another embodiment, a hard gelatin capsule with thicker walls isused. A seal is placed around the capsule to close and seal the N-AcetylMethyl GABA (alone or in combination with surfactants, oils, and/orother ingredients) in the capsule. In an embodiment, a 50/50 (w/w)solution of N-Acetyl Methyl GABA is placed in a single 0 capsule andfilled with about 550 mg of solution for a dose level of 275 mg N-AcetylMethyl GABA per capsule. In double 00 capsules, the fill weight may beabout 800 mg total of such a mixture, including about 400 mg N-AcetylMethyl GABA per dose unit capsule.

“Administering”, “administer” and the like according to the presentinvention refers to providing a composition of the present invention toa subject so that the N-Acetyl Methyl GABA (or its metabolites or othercomponents) reaches the subject's bloodstream and tissues includingbrain tissue and acts to aid sleep, reduce anxiety, treat insomnia, andotherwise as described throughout this application, without being boundby theory. Administration may be by the subject (self-administration) orby another. Administration to the subject may be oral, for instance inthe form of a supplement such as a dietary supplement. Administrationmay be for instance in a solid dosage form, such as a powdered form, ora liquid or semi-liquid form, such as an oil, emulsion, gel, aqueousmixture, suspension, and the like. In an embodiment, administration maybe as a discrete dose unit, for instance encapsulated in a capsule;and/or in a liquid or other form that may be for instance poured orscooped from a bottle, for instance in a 1-2 teaspoon dose.Administration may also be through parenteral, intramuscular,transdermal, topical, sublingual, intravenous, and other physiologicallyacceptable routes.

“Coadministration” and the like according to this invention refers toadministering N-Acetyl Methyl GABA and another drug to a subject, forinstance to further enhance or improve their effects. In an embodiment,a sleep agent such as melatonin is administered with N-Acetyl MethylGABA in a composition to further improve sleep quality and otherovernight characteristics of the drug. In an embodiment, N-Acetyl MethylGABA and melatonin act synergistically to improve qualities and reducesymptoms in a subject. In an embodiment, the N-Acetyl Methyl GABA andadditional drug such as melatonin are formulated together in the samecomposition. In an embodiment, an N-Acetyl Methyl GABA composition and acomposition comprising another drug such as melatonin are administeredwithin a time period allowing them to exert combined effects such asover sleep.

A “subject” according to the present invention is a mammal, such as ahuman, dog, cat, or horse. In an embodiment, a subject is a human. In anembodiment, a human subject is an adult female, an adult male, and/or afemale or male child. A subject may be referred to as a patient.

“Stress” according to the present invention is a feeling of emotional orphysical tension, resulting for instance from an event or thought thatmakes a subject feel frustrated, angry, or nervous. Stress is caused bypressure on a subject to perform, changes and in particular substantialchanges to a subject's environment, and/or fear or worry about an eventoutcome. Stress may be caused for instance by not having enough pressureto perform or challenge in a subject's life. “Anxiety” may be a feelingof fear or apprehension about a current situation or upcoming event, andmay be caused by stress. A subject may rate his or her feelings ofstress or anxiety on a scale of 1 to 5, for instance where 1 is VeryPoor (feeling very stressed and/or anxious), 2 is Poor, 3 is Fair, 4 isGood, and 5 is Excellent (feeling relaxed and with little to no stressor anxiety).

“Sleep quality” according to the present invention refers to how well asubject slept. In an embodiment, a subject or objective observer/deviceassociated with the subject may rate sleep quality by selecting a numberfrom 1 to 5, where 1 is Very Poor (interrupted sleep), 2 is Poor, 3 isFair, 4 is Good, and 5 is Excellent (“sound”, uninterrupted sleep).Sleep quality may be measured for instance by a test administered by aprofessional medical provider or an at-home measurement for instance ofsleep quality parameters by a device, including for instance a cellphone with an application (“app”) for measuring and analyzing asubject's sleep patterns. Sleep quality may also be measured by asubject's experience, as reported by the subject. Good to Excellentsleep quality may be measured for instance as sleeping for instance atleast 80% of the total time in bed (good), or at least 85% of the totaltime (excellent, including 90, 95%, about 100%), or sleeping for moretime in bed after administration of N-Acetyl Methyl GABA than before,preferably statistically significantly more time; falling asleep forinstance in 30 minutes or less; having uninterrupted sleep such as notwaking at all during time in bed or only waking 1 time; after fallingasleep and beginning a sleep period, being awake during the sleep periodfor not more than 15 minutes (excellent) or not more than 30 minutes(good); and/or increasing the duration of the sleep period durationoverall. Improving sleep quality according to this invention may referto increasing a sleep quality rating number after administration ofN-Acetyl Methyl GABA compared with sleep quality reported prior toadministration of N-Acetyl Methyl GABA, for instance from a 2 to a 4. Inan embodiment, good or excellent sleep quality, or improving sleepquality, refers to reducing excessive sleep to a more normal sleepperiod.

A “sleep period” or “period of sleep” according to the present inventionrefers to sleeping for a typical overnight period (for instance a rangeof 6-10 hours, or 7-9 hours, or 7.5-8.5 hours, or about 8 hours, orsimilar range), or for a period of time, for instance, at least 15minutes, at least 30 minutes, at least 45 minutes, at least 1 hour, atleast 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, atleast 6 hours, at least 7 hours, at least 8 hours, at least 9 hours, orat least 10 hours; and any range of any of these periods, for instancefrom 15 minutes to 10 hours. In an embodiment, a sleep period may belonger than indicated above, for instance up to 11 hours or up to 12hours. Reference to “in bed” is to a place for the subject to sleep upon(bed, sofa, cushions, and so forth for instance for a human subject),preferably in a prostrate/lying down position but including a sitting orreclined position. References to “overnight” may be to a sleep periodduring nighttime for the subject, or to a different time period duringthe day, for instance as experienced by third shift workers.

A “good” or “excellent” period of sleep in a subject according to thepresent invention refers to a period of sleep for instance rated as goodor excellent by the subject and/or by an objective rating such as by adevice or observer. In an embodiment, a good or excellent period ofsleep may include having improved sleep quality over a prior sleepperiod; as well as good or excellent, and/or improved,restfulness/wakefulness; good or excellent, and/or improved, mentalclarity/memory; good or excellent, and/or improved, mood; and/or good orexcellent, or improved, reduction of inflammation and/or pain, after thesleep period.

“Restfulness/Wakefulness” according to the present invention refers to asubject's report of how well-rested, awake, and/or energetic the subjectfelt after a sleep period, for instance by selecting a number from 1 to5, where 1 is Very Poor (Groggy/Slow to Respond/Sleepy), 2 is Poor, 3 isFair, 4 is Good, and 5 is Excellent (Wide Awake/Energetic). In anembodiment, the report may be by observation by an observer, such as adevice or person including for instance a medical observer. Improvingrestfulness/wakefulness according to this invention refers to increasingthe selected number, for instance from a 1 to a 3, when N-Acetyl MethylGABA is administered in an effective amount prior to sleeping. Achievinggood or excellent restfulness/wakefulness refers to a subject that feelsrested, awake, and/or energetic after sleeping; in contrast to feelingfor instance groggy, sleepy, lethargic. In an embodiment, theadministration of an effective amount of N-Acetyl Methyl GABA accordingto this invention may also improve restfulness and/or wakefulness withor without a period of sleep.

“Mental Clarity/Memory” according to the present invention refers to asubject's report on his or her ability to focus on important matters,and/or recall immediate tasks at hand, for instance by selecting anumber from 1 to 5, where 1 is Very Poor (Confused/Unfocused/Unable toConcentrate), 2 is Poor, 3 is Fair, 4 is Good, and 5 is Excellent(Clear/Focused/Able to Concentrate). an embodiment, the report may be byobservation by an observer, such as a device or person including forinstance a medical observer. Improving mental clarity/memory accordingto this invention refers to increasing the selected number, for instancefrom a 3 to a 4, when N-Acetyl Methyl GABA is administered in aneffective amount prior to sleeping. Achieving good or excellent mentalclarity/memory refers to a subject that feels alert and able to focus ontasks at hand. In an embodiment, the administration of an effectiveamount of N-Acetyl Methyl GABA according to this invention may alsoreduce anxiety and/or improve a subject's mental clarity with or withouta period of sleep.

“Mood” according to the present invention refers to a subject's reportof the subject's perceived emotional state for instance after a periodof sleep, for instance a number from 1 to 5, where 1 is Very Poor(Irritable or sad/depressed), 2 is Poor, 3 is Fair, 4 is Good, and 5 isExcellent (Happy/Serene). an embodiment, the report may be byobservation by an observer, such as a device or person including forinstance a medical observer. Improving mood according to this inventionrefers to increasing the selected number, for instance from a 2 (poormood) to a 3 (fair mood), when N-Acetyl Methyl GABA is administered inan effective amount prior to sleeping. Achieving a good or excellentmood refers to a subject that feels happy and satisfied after a periodof sleep, for instance and preferably an overnight sleep. In anembodiment, the administration of an effective amount of N-Acetyl MethylGABA according to this invention may reduce irritability and/or improvea subject's mood with or without a period of sleep.

“Inflammation and Pain Reduction”, “Body Aches and Pains”, and the likerefers to inflammatory processes of the body and pain or discomfortassociated with them. Inflammatory processes of the body may be reducedduring sleep, and in particular during good or excellent sleep.Reduction of inflammation and pain may be rated by the subject orassociated device as existing and/or reduced for instance as 1 (mostinflammation and pain), 2 (inflamed and painful), 3 (somewhat inflamedand painful), 4 (little inflammation and pain), 5 (almost no or noinflammation and pain). In an embodiment, the report may be byobservation by an observer, such as a device or person including forinstance a medical observer. In an embodiment, reducing inflammation andpain in a subject relates to an increase in the number selected to rateinflammation and pain. In an embodiment, the administration of aneffective amount of N-Acetyl Methyl GABA according to this invention mayalso reduce stress, reduce inflammation, and/or reduce pain with orwithout a period of sleep.

“Insomnia” according to the present invention refers to an inadequatesleep period such as an overnight sleep period, with the subject wakingwith tiredness, lack of energy, difficulty concentrating, irritablemood, and so forth, for instance as indicated above in the “Very Poor”or “Poor” categories of Sleep Quality, Restfulness/Wakefulness, MentalClarity/Memory, and/or Mood. an embodiment, the report may be byobservation by an observer, such as a device or person including forinstance a medical observer. In an embodiment, insomnia refers to poorsleep quality such as difficulty falling asleep, interruptedsleep/waking frequently during the night, difficulty (e.g inability orlengthy time period) returning to sleep, waking too early, and/orunrefreshing sleep. In an embodiment, insomnia is treated with N-AcetylMethyl GABA according to the present invention by improving one or moreaspect of poor sleep quality. Such improvement may be measured by arating system for instance of 1 to 5 as discussed above. In anembodiment, insomnia is temporary or situational insomnia. In anembodiment, insomnia according to this invention is chronic insomnia.

“Daytime Energy” according to the present invention may be measured by asubject's rating on a scale of 1 to 5 of feeling for instance 1 (“VeryPoor), not feeling energetic during the day), 2, 3, 4, through 5(“Excellent”, feeling energetic during the day).

The present invention may be further understood in connection with thefollowing Examples and embodiments. The following non-limiting Examplesand embodiments described throughout this application are provided toillustrate the invention. Generally, chemical steps may be performed inany order, unless indicated otherwise.

EXAMPLES Example 1—Synthesis and Purification of N-Acetyl Methyl GABA

Example 1 shows how to provide high yield, easily separable, N-AcetylMethyl GABA according to the present invention, in a fairly pure state.Step 2 in particular was difficult to develop. Most acetylations usingacetyl chloride use pyridine as a solvent and use trimethylamine andsodium acetate as bases. Two problems arose with these conditions. One,the yield was very low (about 5%). The second problem was in trying toextract the desired finished product from the pyridine. Di-ethyl etherextraction of acidified pyridine in water resulted in a low yield, andthe residual pyridine which is very unpleasant to smell was not removed.CARTER et al., “1.Azlactones:III.Acylation of Amino Acids in Pyridine”J. Biol. Chem. 138:619-626 (1941).

The next method used a brine solution with sodium acetate andtrimethylamine. The acetylation was performed with 50% acetyl chloridein acetone. After reaction, it was acidified with HCl and neutralizedwith trimethylamine, then extracted with 2 volumes of methylenechloride. After drying under vacuum, the yield was only 10% product, andtan in color, which indicated it was not pure. BASU et al., “Efficientacetylation of primary amines and amino acids in environmentally benignbrine solution using acetyl chloride” J. Chemical Sci. 125(3):607-613(2013).

Next, iodine crystals were tried, as disclosed by PHUKAN et al., “Mildand Useful Method for N-Acylation of Amines” Synthet. Comms.39(15):2694-2701 (2009). The need to add sodium thiosulfate toneutralize the iodine was messy. Also, an extraction step was needed,which lowered the yield, and required a solvent that would have to bedistilled to be recovered.

Next, acetylation was carried out using acetyl chloride in varioussolvents: DMF, DMSO, methylene chloride, acetonitrile, and ethylacetate. The problem with this method was that the potassium carbonatewas not always soluble to react properly and the solvents used hadnegative side effects and blocked recovery. Recovery would be difficultbecause the ester being prepared is like a solvent, and trying toextract it with a solvent, trying to either dry it under vacuum ordistillation, was difficult. The boiling point of N-Acetyl Methyl GABAis about 65° C., and difficult to separate from solvents with a similarboiling point. DARSI et al., “Studies on N-acetylation of Anilines withAcetyl Chloride using Phase Transfer Catalysts in Different Solvents”Der Pharma Chemica 3(5):35-38 (2011).

After attempting the above methods and reviewing many others, twofactors became important for a preferred method of the presentinvention. (1) A basic or neutral pH (preferably within a pH range of6.5-8) needs to be maintained for the acetylation reaction work well.(2) A solvent which works and has a lower boiling point than N-AcetylMethyl GABA is necessary, and preferably is inexpensive. The solventshould be safe to handle and to recover. In an embodiment, acetone is asolvent useful in step (2) of this invention.

Synthesis Reagents:

GABA was supplied by Stryka Botannics, 279 Homestead Road, Hillsborough,NJ 08844, USA

HPLC Grade Methanol, Catalog #33900HPLC, was provided by GreenfieldGlobal, 58 Vale Road, Brookfield, CT 06804, USA

HPLC Grade Acetone, Catalog #9003-03, Mallinckrodt-Baker Inc.,Phillipsburg, NJ 08865, USA

Hydrogen Chloride Anhydrous GAS Catalog #UN1050, Praxair Inc. Danbury CT06810-6266, USA

Acetyl Chloride 98%, Thermo Fisher Scientific, Shore Road, Port ofHeysham, Lancashire, LA32KY, UK

Sodium Bicarbonate USP Grade #1, VITUSA Products, 343 Snyder Ave.,Berkeley Heights, NJ 07922 USA

Synthesis Steps 1-3 below must be performed in order.

Step 1: Synthesis of Methyl GABA

In this step, the polar carboxyl (—C(O)OH) end of GABA(NH₂CH₂CH₂CH₂C(O)OH) was methylated to become —C(O)OCH₃ (“Methyl GABA”NH₂CH₂CH₂CH₂C(O)OCH₃), as follows:

GABA (300 grams) was added to 10 volumes of reagent methanol (3000 ml)in a boiling flask and then in a fume hood. Preferably, there is about10 times the amount of methanol in order to bring the GABA intosolution. Smaller amounts were tried but the yield was lower. AnhydrousHCl was bubbled in the mixture while stirring until the GABA wascompletely in solution. Boiling chips were added. The solution wasrefluxed overnight using a condenser at the boiling point of methanol(64.7° C.). The methanol was distilled off. A yield of nearly 100%Methyl GABA was achieved based on theoretical weight.

Step 2: Synthesis of N-Acetyl Methyl GABA

In this step, the polar amino (—NH₂) end of Methyl GABA is acetylated tobecome —NH—C(O)CH₃ (“N-Acetyl Methyl GABA”). The Methyl GABA is a clearviscous syrup in nearly 100% yield. This was determined by yield weight.

The remaining viscous liquid was poured into a 5000 mL beaker whilestill warm. 3000 mL of acetone was added and stirred. Then 631 gramssodium bicarbonate was added, a small scoop at a time to prevent thereaction from producing too much carbon dioxide and overflowing thebeaker. This step removes the HCL from the GABA so that the reaction mayproceed. Sodium bicarbonate was used to maintain the pH range between6.5-8. The beaker was placed on a magnetic stirrer. An extraction funnel(500 mL) with 338 g (307 mL) acetyl chloride was put in place to add theacetyl chloride drop-wise to the mixture in the beaker.

Normally, acetyl chloride reactions tend to be violent and exothermic,but this reaction is calm and predictable. Without being bound bytheory, the sodium bicarbonate is solubilized by the water that isproduced by the reaction which reacts with the HCl attached to the aminogroup of the Methyl GABA. This opens up the site so the acetyl group canattach itself to the Methyl GABA. The freed HCl then reacts with thebicarbonate to form sodium chloride or salt and the CO₂ comes off as agas. The solution warmed to about 40° C. during the process and bubblesformed on the top and then dissipated. The solution was covered andallowed to stir for 4 hours or until the reaction ceased. The salt wasfiltered from the solution and the filtrate was placed in a clean 5000mL boiling flask and boiling stones added. The acetone was boiled offfrom 52° C. to 60° C. and then the N-Acetyl Methyl GABA was distilledoff in clear, nearly pure form into a 2000 mL boiling flask. Thesolution was collected up to 78° C. The yield was about 440 g of atheoretical total of 515 g (85%). This crude distillate was about 95%pure N-Acetyl Methyl GABA by gas chromatograph (0.2 ul actual injectionvolume, Agilent, Santa Clara, CA), as shown in the gas chromatogramrepresented in FIG. 1 . The second peak that elutes (2.385) is N-AcetylMethyl GABA at about 95%.

TABLE 1 FT-IR Scan Area Percentage Report Peak Retention Width Area AreaPeak Time (min) Type (min) (pA*s) (%) 1 1.722 BB S 0.0246 1.38594e43.30003 2 2.385 VB S 0.0433 3.99239e5 95.06185 3 2.628 BV T 0.04336879.74023 1.63812 4 8.177 0.0000 0.00000 0.00000 5 8.972 0.0000 0.000000.00000 6 9.955 0.0000 0.00000 0.00000 TOTAL: 4.19978e5

Step 3: Purification of N-Acetyl Methyl GABA

The crude distillate of Step 2 was applied to a high purity distillationunit to yield nearly 100% N-Acetyl Methyl GABA, as shown in FT-IR(Fourier-Transform Infrared Spectroscopy) (Shimadzu IRTracer-100,Shimadzu Scientific Instruments, Columbia, MD) scan of FIG. 2 (data inTable 1). The FT-IR scan shows expected energy bands and very littlenoise denoting nearly pure product. N-Acetyl Methyl GABA is a clearliquid and it has a distinct odor slightly different from ethyl acetate.Acetone and methanol can be recovered. Only a small residual solventneeds to be discarded.

Example 2 In Vivo Studies

Table 2 reports a human female subject's sleep quality,restfulness/wakefulness, mental clarity/memory, mood, and inflammationand pain reduction after 18 overnight sleep periods over the span of 15weeks (October-January, as shown in Table 2), with 15 of the 18 nightsoccurring before the first administration of N-Acetyl Methyl GABA to thesubject. Table 3 reports the subject's sleep quality and otherparameters after self-administering 300 mg of N-Acetyl Methyl GABAbefore an overnight sleep period, 40 times over the span of 9 weeks(November-January, as shown in Table 3). Data in Tables 2 and 3 arebased on a rating of sleep quality and other parameters from 1 to 5,where 1 is Very Poor, 2 is Poor, 3 is Fair, 4 is Good, and 5 isExcellent. Each morning after waking, the subject reported on the sleepquality, restfulness/wakefulness, mental clarity/memory, mood, andinflammation and pain reduction they felt, and/or with regard to sleepquality, used information from a “Sleep Cycle” app on a cell phone(Sleep Cycle, www.sleepcycle.com, Gothenburg, Sweden).

TABLE 2 Subject report on overnight sleep with no administration ofN-Acetyl Methyl GABA (NAMGABA) 1: Very Poor 2: Poor 3: Fair 4: Good 5:Excellent Antinflam- matory Mental Action NAMGABA Sleep Restfulness/Clarity/ (decrease Administered? Quality Wakefulness Memory Mood inpain) Oct. 13, 2019 No NAMGABA 1 1 2 1 1 Oct. 14, 2019 No NAMGABA 2 1 22 2 Oct. 15, 2019 No NAMGABA 3 2 2 2 2 Oct. 18, 2019 No NAMGABA 2 1 2 12 Oct. 21, 2020 No NAMGABA 2 2 2 2 2 Oct. 22, 2019 No NAMGABA 2 1 2 2 2Oct. 23, 2019 No NAMGABA 3 2 3 2 2 Oct. 29, 2019 No NAMGABA 2 2 3 1 1Oct. 31, 2019 No NAMGABA 1 1 2 1 1 Nov. 3, 2019 No NAMGABA 3 2 2 2 1Nov. 4, 2019 No NAMGABA 2 3 2 2 2 Nov. 10, 2019 No NAMGABA 3 2 2 3 2Nov. 17, 2019 No NAMGABA 2 1 2 3 1 Nov. 18, 2019 No NAMGABA 2 2 2 3 2Nov. 19, 2019 No NAMGABA 1 2 2 1 1 Nov. 26, 2019 No NAMGABA 3 3 2 2 2Jan. 17, 2020 No NAMGABA 3 4 2 2 3 Jan. 26, 2020 No NAMGABA 3 4 3 3 3Total Score 40 36 39 35 32 18 Days Average without 2.2 2 2.2 1.9 1.7taking N-Acetyl Methyl GABA

TABLE 3 Subject report on overnight sleep after administration ofN-Acetyl Methyl GABA 1: Very Poor 2: Poor 3: Fair 4: Good 5: ExcellentRest- Antinflammatory fulness/ Mental Action Sleep Wake- Clarity/(decrease in Quality fulness Memory Mood pain) Nov. 20, 2020 5 4 4 4 2Nov. 21, 2019 4 3 3 3 3 Nov. 24, 2019 5 4 4 4 3 Nov. 25, 2019 5 4 4 4 4Dec. 1, 2019 5 4 4 3 2 Dec. 2, 2019 5 4 4 4 3 Dec. 4, 2019 5 5 4 4 3Dec. 5, 2019 5 5 4 3 2 Dec. 8, 2019 4 5 5 4 3 Dec. 9, 2019 5 5 5 4 3Dec. 11, 2019 5 5 5 5 4 Dec. 15, 2019 5 5 5 4 3 Dec. 16, 2019 4 4 4 5 4Dec. 17, 2019 5 5 5 5 4 Dec. 18, 2019 5 5 5 5 4 Dec. 20, 2019 5 5 5 5 4Dec. 25, 2019 5 5 5 4 4 Dec. 26, 2019 5 5 5 5 4 Dec. 28, 2019 4 5 5 5 4Dec. 29, 2019 5 5 4 5 4 Dec. 30, 2019 4 4 4 5 4 Jan. 1, 2020 4 4 5 5 4Jan. 2, 2020 5 5 4 4 4 Jan. 4, 2020 5 5 4 5 4 Jan. 5, 2020 5 5 4 5 5Jan. 6, 2020 5 5 5 5 5 Jan. 7, 2020 4 4 4 5 4 Jan. 8, 2020 5 4 4 5 4Jan. 9, 2020 4 4 5 5 5 Jan. 11, 2020 5 5 4 5 5 Jan. 12, 2020 5 5 4 5 5Jan. 13, 2020 5 4 4 3 3 Jan. 14, 2020 5 4 5 4 4 Jan. 15, 2020 5 4 4 4 4Jan. 16, 2020 5 5 5 4 4 Jan. 19, 2020 5 5 4 4 4 Jan. 20, 2020 4 4 4 4 4Jan. 21, 2020 4 5 5 5 5 Jan. 22, 2020 5 5 5 4 4 Jan. 23, 2020 5 5 5 5 5Total Score, 40 190 183 177 176 153 days Average With 4.7 4.6 4.4 4.43.8 N-Acetyl Methyl GABA

TABLE 4 Summary of subject reports before and after administration ofN-Acetyl Methyl GABA 1: Very Poor 2: Poor 3: Fair 4: Good 5: ExcellentAnti- Rest- inflammatory fulness/ Mental Action Sleep Wake- Clarity/(decrease in Quality fulness Memory Mood pain) Without N- 2.2 2 2.2 1.91.7 Acetyl Methyl GABA, average score With N-Acetyl 4.7 4.6 4.4 4.4 3.8Methyl GABA, average score Improvement +2.5 +2.6 +2.2 +2.5 +2.1 aftertaking N-Acetyl Methyl GABA

Discussion:

The subject of Example 2 reported improved sleep quality and othertested parameters after self-administration of N-Acetyl Methyl GABAprior to an overnight sleep period. For 14 of the days reported in Table2, before the first administration of N-Acetyl Methyl GABA, data is froma sleep app on a cell phone device. Other data in Table 2 is from thesubject's experience as reported for a given sleep period. The databefore first administration of N-Acetyl Methyl GABA provides a baselineof sleep patterns for the subject with no sleep aid. The average sleepquality in the subject before a first administration of N-Acetyl MethylGABA was 73.8%. The average percentage of sleep quality improved afteradministration of N-Acetyl Methyl GABA according to this invention, withaverage sleep quality at 80.4%. The subject also reported no longerfeeling morning or mid-afternoon anxiety, and having better mentalclarity and clearer focus, after waking from the sleep periods. No sideeffects from the administration of N-Acetyl Methyl GABA were reported bythe subject.

Table 4 represents average data from Tables 2 and 3, and provides animprovement score for parameters studied after taking N-Acetyl MethylGABA. As shown in Table 4, sleep quality during overnight sleep periodsfor the subject without N-Acetyl Methyl GABA was on average 2.2, or“Poor” to “Fair” on average. After taking N-Acetyl Methyl GABA, sleepquality during overnight sleep periods for the subject was on average4.7, or “Good” to “Excellent”. On average, sleep quality for the subjectimproved by 2.5, or approximately 115% (2.5/2.2*100%).

The subject's restfulness/wakefulness was rated on a scale of 1 to 5 asdiscussed above, after an overnight sleep period with no administrationof N-Acetyl Methyl GABA (Table 2) and with administration of N-AcetylMethyl GABA (Table 3). As shown in Table 4, the subject ratedrestfulness/wakefulness after sleep periods without N-Acetyl Methyl GABAas 2, “Poor”, on average; with N-Acetyl Methyl GABA,restfulness/wakefulness was rated at 4.6, or “Good” to “Excellent”. Onaverage, restfulness/wakefulness after sleep periods with N-AcetylMethyl GABA improved by 2.6 on the rating scale, or 130% (2.6/2*100%).

The subject's mental clarity/memory was rated on a scale of 1 to 5 asdiscussed above, after an overnight sleep period with no administrationof N-Acetyl Methyl GABA (Table 2) and with administration of N-AcetylMethyl GABA (Table 3). As shown in Table 4, on average the subject ratedmental clarity/memory after sleep periods without N-Acetyl Methyl GABAas 2.2, “Poor” to “Fair”; with N-Acetyl Methyl GABA, mentalclarity/memory was rated at 4.4, or “Good” to “Excellent”. On average,mental clarity/memory after sleep periods with N-Acetyl Methyl GABAimproved by 2.2 on the rating scale, or by 100% (2.2/2.2*100%).

The subject's mood was rated on a scale of 1 to 5 as discussed above,after an overnight sleep period with no administration of N-AcetylMethyl GABA (Table 2) and with administration of N-Acetyl Methyl GABA(Table 3). As shown in Table 4, on average the subject rated mood aftersleep periods without N-Acetyl Methyl GABA as 1.9, “Very Poor” to“Poor”; with N-Acetyl Methyl GABA, the subject's mood rated at 4.4, or“Good” to “Excellent”. On average, the subject's mood after sleepperiods with N-Acetyl Methyl GABA improved by 2.5 on the rating scale,or by about 132% (2.5/1.9*100%).

Before administration of N-Acetyl Methyl GABA, the subject reportedhigher levels of inflammatory conditions on a daily basis, andconsequent pain/discomfort. The subject's inflammation/pain was rated ona scale of 1 to 5 as discussed above, after an overnight sleep periodwith no administration of N-Acetyl Methyl GABA (Table 2) and withadministration of N-Acetyl Methyl GABA (Table 3). As shown in Table 4,on average the subject rated inflammation/pain after sleep periodswithout N-Acetyl Methyl GABA as 1.7, “Very Poor” to “Poor”. WithN-Acetyl Methyl GABA, the subject's inflammation/pain rated at 3.8, or“Fair” to “Good”. On average, the subject's inflammation/pain aftersleep periods with N-Acetyl Methyl GABA improved by 2.1 on the ratingscale, or by about 125% (2.1/1.7*100%).

The administration of N-Acetyl Methyl GABA to other human subjectsaccording to this invention has been well tolerated to date. Subjectsreport improved sleep quality when N-Acetyl Methyl GABA is administeredprior to a sleep period, and next day, improved memory and mentalclarity, improved restfulness and well-being, improved mood, anddecreased inflammation and pain. Subjects report more natural sleepwithout the morning grogginess associated with many sleep aids. Subjectsreport they slept all night long without waking. Subjects report thatgeneral body inflammation and aches and pains were also reduced whenN-Acetyl Methyl GABA was administered prior to an overnight sleepperiod. Subjects report the mind is clear and the attitude is positiveafter N-Acetyl Methyl GABA was administered prior to an overnight sleepperiod. Without being bound by theory, this may be due to anxiolyticeffects of N-Acetyl Methyl GABA.

Example 3

An embodiment of an emulsion of a liposome that may be provided foradministration according to this invention is set out in Table 5, below.

TABLE 5 N-Acetyl Methyl GABA Composition % composition Ingredient MG,IU, ML added (w/w) Deionized Water 5595.0 ml 70.0% Glycerine USP 1162.0ml 14.5% Soy Lecithin Liquid 565.0 ml 7.1% N-Acetyl Methyl GABA 300.0 mg3.8% Orange Flavor Liquid 100.0 ml 1.3% Sodium Lauroyl Lactylate 80.0 mg1.0% Stevia Extract 90% 30.0 ml 0.38% Bitter Mask Powder 28.0 mg 0.35%Luo Han Guo 50% 28.0 ml 0.35% Guar Gum (Cosmetic Grade) 25.0 mg 0.31%Potassium Sorbate (Granular) 22.0 mg 0.28% Curcumin 95% 20.0 mg 0.25%Vitamin E Oil 18.0 ml 0.22% Peppermint Oil 10.0 ml 0.125% Cinnamon(Cassia) Oil 10.0 ml 0.125% Melatonin 5.0 mg 0.06% DOSE WEIGHT 7.998 gTOTAL: 100% (rounded)

The above composition of the present invention is preferably shaken wellbefore administration. The composition is for oral administration. In anembodiment, the composition promotes healthy sleep, helps manage stressand anxiousness, and may be taken for instance 30 minutes before bedtime(i.e. an overnight sleep period). Active ingredient N-Acetyl MethylGABA, along with melatonin are formulated in a base of purified water,glycerine, soy lecithin, natural and artificial orange flavor, sodiumlauroyl lactylate, Stevia extract, potassium sorbate (preservative), LuoHan Guo Extract, Guar gum, Curcumin extract, Vitamin E Oil, PeppermintOil, Cinnamon Oil. In an embodiment, the ingredients combine to weight 8g, volume approximately 2 tsp, as 1 serving size. In an embodiment, theserving size includes an effective amount of about 300 mg N-AcetylMethyl GABA. In an embodiment, a dose of 1-2 serving sizes is takenbefore bedtime. In an embodiment, larger serving sizes, such as 3 ormore serving sizes, may be taken by a human subject. In an embodiment,the composition has a strong cinnamon/mint flavor and very little aftertaste. The N-Acetyl Methyl GABA has a strong solvent like taste similarto ethyl acetate, which can be difficult to mask, and is preferablymasked for instance as in the composition discussed above. Strongflavors are preferred accordingly in compositions of the presentinvention.

Examples 4 and 5 Study Purpose:

The purpose of this study was to quantify the effectiveness of N-AcetylMethyl GABA with sleep and related symptoms and qualities. Without beingbound by theory, it is believed that standard GABA cannot cross theblood brain barrier. N-Acetyl Methyl GABA is believed to cross the bloodbrain barrier and act directly upon the CNS.

N-Acetyl Methyl GABA Composition:

The composition described in Table 6 was taken orally by each patientonce daily before an overnight sleep period.

TABLE 6 N-Acetyl Methyl GABA composition MGS-IU- % COMPOSITION RM# TYPEINGREDIENT ML ACT % OV GMS-ML (W/W) 212 A DEIONIZED WATER 4970.0 1.00 04.9700 62.1%  209 A GLYCERINE USP 1181.0 1.00 0 1.1810 14.8%  3540 A MCTOIL 60/40 465.0 1.00 0 0.4650 5.8% 2707 A A-SOY LECITHIN LIQUID 400.01.00 0 0.4000 5.0% 3659 A N-ACETYL METHYL GABA 300.0 0.95 5 0.3316 3.8%2015 A ORANGE FLAVOR LIQ 186.0 1.00 0 0.1860 2.3% 1829 A XYLITOLGRANULAR (FINE) 150.0 1.00 0 0.1500 1.9% 3490 A SODIUM LAUROYL 56.0 1.000 0.0560 0.7% LACTYLATE 1348 A STEVIA EXT 90% 46.0 1.00 0 0.0460 0.6%2108 A BITTER MASK POWDER 46.0 1.00 0 0.0460 0.6% 30-09 3635 A LUO HANGUO 50% 46.0 1.00 0 0.0460 0.6% 268 A PEPPERMINT OIL 33.0 1.00 0 0.03300.4% 2053 A GUAR GUM (COSMETIC 24.0 1.00 0 0.0240 0.3% GRADE) 384 ACINNAMON (CASSIA) OIL 24.0 1.00 0 0.0240 0.3% 255 A POTASSIUM SORBATE20.0 1.00 0 0.0200 0.25%  (GRAN) 298 A VITAMIN E OIL 18.0 1.00 0 0.01800.23%  1308 A MELATONIN 5.0 1.00 0 0.0050 0.06%  DOSE WEIGHT = 8.002GRAMS 8 g 100%  (rounded)

Subjects were administered 2 teaspoons (8 g) of the liquid N-AcetylMethyl GABA composition described above approximately 30 minutes beforegoing to bed.

Study Design:

Study participants:

-   -   Group 1: 15 subjects (human)    -   Group 2: 31 subjects (human)

Duration:

7 day pre-study symptomatology (no N-Acetyl Methyl GABA (NAMG) taken) torecord a baseline of patient symptoms.

14 day study symptomatology (taking N-Acetyl Methyl GABA) to recordpatient symptoms.

Criteria for Eligibility:

Age requirements: Anyone over the age of 12 was eligible to participatein the study.

Type of Patient:

Preferred subject would have minimum two of the following symptoms priorto study: Sleep imbalance; insomnia; anxiety; mood issue; stress; mentalclarity, memory and/or focus issues; daytime energy issues; body achesand pains; digestive issues; stress headaches.

Subjects were not asked to alter their normal life habits such asdrinking alcohol, smoking or caffeine before going to sleep.

Medications:

Subjects were asked to not use additional natural supplements other thanthe N-Acetyl Methyl GABA composition for sleep during the 14 day study.

Subjects were allowed to stay on any current medications they were on,if any, and to note the medications. One Group I patient reported takingbenzodiazepine during the study and was not asked to discontinue use.

All subjects reported that they did adhere to protocol.

Tables 7, 8 and 9 show patient outcomes for Groups 1 and 2. Ratings weremade each day during the study period (7 days pre-administration,14-days during N-Acetyl Methyl GABA administration), based on a scale of1 to 5. Improvements are shown by increased ratings in qualities such asSleep Quality, Restfulness/Wakefulness, Mental Clarity/Memory, Mood,Daytime Energy are shown for each patient in Table 7, as are reductionsin symptoms such as stress, anxiety, body aches/pain, stress headaches,and digestive issues. The 5 far-right columns refer to waking andfalling back asleep during an overnight sleep period. Patient gender andage for Table 7 is as follows: Patient 1 (P1): M/age 32, P2: M/28,P3:F/22; P4:F/49, P5:M/54, P6:F/32, P7:M/35, P8:M/56, P9:F/47, P10:M/38,P11:F/68, P12:F/34, P13:M/26, P14:M/44, P15:F/20. Similarly for Tables 8and 9, improved qualities, reduced symptoms, and overnight sleep perioddetails are shown as a percentage over baseline qualities and symptoms.Patient gender and age for Table 8 is as follows: Patient 1 (P1): M/70,P2:F/47, P3:F/69, P4:F/49, P5:M/51, P6:F/28, P7:F/66, P8:F/53, P9: M/59,P10:M/38, P11:M/31, P12:F/29, P13:M/73, P14:F/47, P15:M/56, P16:F/59,P17:M/34, P18:F/73, P19:F/62, P20:M/61, P21:F/62, P22:F/63, P23:F/62,P24:F/22, P25:M/34, P26:M/19, P27:F/27, P28:F/31, P29:M/39, P30:M/69,P31:F/47.

TABLE 7 Nighttime Study, 15 Human Patient Outcomes Mental Body SleepRestfulness/ Clarity/ Daytime Aches/ Stress Quality Wakefulness MemoryMood energy Stress Anxiety Pain Headaches Patient # Improved ImprovedImproved Improved Improved Reduced Reduced Reduced Reduced (Gender/Age)(%) (%) (%) (%) (%) (%) (%) (%) (%) 1 78 60 74 124 124 83 93 87 100 2 38107 106 115 100 119 92 72 124 3 123 155 115 170 130 93 134 124 178 4 116133 169 288 195 143 180 210 113 5 88 122 119 150 114 114 160 68 258 6119 115 40 51 68 47 93 40 33 7 70 87 45 79 72 77 142 43 92 8 65 89 79192 167 133 180 56 211 9 89 31 133 65 124 68 100 40 −5 10 88 64 56 163126 94 83 22 195 11 49 43 33 124 94 47 27 37 0 12 133 17 24 100 100 50180 −13 100 13 63 86 200 155 180 79 121 47 0 14 46 112 22 84 67 87 10019 81 15 119 14 62 169 60 50 312 40 0 Time to Falling Fall OverallDigestive Waking Waking Back to Back to Sleep Issues (overall) (# times)Sleep Sleep Duration Patient # Reduced Reduced Reduced Improved ReducedIncreased (Gender/Age) (%) (%) (%) (%) (%) (%) 1 59 245 934 100 540 19.52 44 245 245 NA* NA* 29 3 108 178 456 20 167 17 4 76 376 376 376 968 255 79 100 300 100 1373 24 6 0 133 365 NA* NA* 15 7 24 NA* NA* NA* NA* 8 859 133 365 133 736 12 9 30 133 133 133 740 46 10 14 0 100 0 478 18 11 270 0 0 202 18 12 15 178 178 178 520 8 13 21 75 75 75 336 17 14 17 614 614NA* NA* 10 15 14 100 376 35 499 12 *Patient reported that duringbaseline when patient woke, could not fall back to sleep.

TABLE 8 Nighttime Study, 31 Patient Outcomes Mental Body SleepRestfulness/ Clarity/ Daytime Aches/ Stress Digestive QualityWakefulness Memory Mood Energy Stress Anxiety Pain Headaches IssuesStudy Dates Improved Improved Improved Improved Improved Reduced ReducedReduced Reduced Reduced Patient # (2020) (%) (%) (%) (%) (%) (%) (%) (%)(%) (%) 1  11/2-11/22 37 37 33 58 68 37 37 53 88 68 2  11/2-11/22 75 4345 45 48 60 19 70 71 33 3  11/2-11/22 61 79 60 77 83 115 57 11 34 0 4 11/2-11/22 12 45 40 82 62 70 27 42 74 55 5  11/2-11/22 106 115 81 12237 144 40 0 0 40 6  11/2-11/22 75 85 115 60 52 81 107 20 0 0 711/16-12/6  40 48 117 122 122 83 129 30 122 5 8 11/16-12/6  110 95 81100 100 135 65 33 91 27 9 11/16-12/6  60 131 106 134 70 92 51 36 100 2710 11/16-12/6  89 148 146 152 159 118 127 10 110 73 11 11/18-12/8  107106 64 167 92 134 180 4 93 0 12 11/25-12/15 215 93 93 94 82 182 184 29343 15 13 11/23-12/13 143 101 43 81 65 126 157 60 177 33 14 11/23-12/1350 112 89 134 43 118 75 50 87 40 15 11/23-12/13 134 87 112 134 43 88 6046 173 4 16 11/25-12/15 100 93 184 100 112 121 117 77 188 15 1711/12-12/2  134 100 118 150 100 180 56 12 81 11 18 11/19-12/9  92 50 6568 100 61 65 0 0 0 19 11/23-12/13 96 75 31 72 40 39 133 93 81 55 2011/23-12/13 64 66 43 43 33 75 0 13 29 0 21 11/23-12/13 69 33 57 22 27 3734 75 25 0 22 11/25-12/15 81 59 81 40 55 69 27 52 100 38 23 11/25-12/1575 112 100 70 66 180 148 121 87 75 24 11/11-12/1  69 121 134 144 100 107200 40 148 33 25 11/11-12/1  115 148 94 205 0 78 100 0 133 29 2611/11-12/1  89 50 33 133 22 72 65 32 121 31 27 11/28-12/18 52 121 40 15043 36 87 4 100 0 28 11/27-12/17 67 50 8 75 14 40 180 0 110 0 2911/16-12/6  67 150 79 192 89 87 367 50 180 50 30 11/14-12/4  35 27 59 9327 33 27 13 45 10 31  11/5-11/25 79 94 32 118 40 58 62 17 94 8

TABLE 9 Changes in Common Sleep Parameters in Group 2 Subjects AverageBaseline Average # To Fall Back Asleep Average Baseline Waking In TimesWoken DECREASED of Sleep per night Middle in Middle of before/duringbefore/during of Night Night study by (min) study (hours) DECREASEDDECREASED Before After Before After Patient by (%) by (%) NAMG NAMG NAMGNAMG 1 100 300 22.14 5.64 5.64 6.39 2 0 0 35 8.57 5.86 6.32 3 75 7552.86 14.64 5.79 6.39 4 0 0 30 16.07 7 7.61 5 0 0 38.57 17.43 6.64 7.646 0 0 49.29 20 5.5 6.29 7 100 200 6.43 0 5.64 6.64 8 41 41 0 0 6.5 7.189 207 207 8.57 0.71 7.29 7.93 10 56 56 35 10.71 6.07 7.29 11 307 51421.43 1.43 6.5 7.61 12 56 590 30.71 3.57 6.86 7.89 13 27 27 15.71 5 6.57.29 14 (NA) (NA) (NA) (NA) 7 7.79 15 16 16 19.29 6.07 7.5 8 16 132 43335 4.29 7 7.82 17 178 217 27.86 5 7.14 7.82 18 0 77 30 11 7 7.96 19 0286 51.43 18.21 6 6.32 20 178 456 25 3.57 5 5.96 21 0 129 60 6.79 6 6.6422 0 146 53.57 8.93 5.5 6.89 23 0 110 132.86 33.93 5.86 6.93 24 41 41 304.29 6.5 7 25 133 165 37.14 2.86 6.93 7.29 26 16 50 25.71 8.57 7 7.21 27100 300 39.29 6.79 6.5 7.36 28 133 303 52.86 7.5 5.79 7.25 29 16 4729.29 13.21 6 6.89 30 133 75 8.57 7.14 5.57 6.46 31 41 283 60 14.64 4.796.25 *Did not wake during night **Subject reported once awake, staysawake

Table 10 shows a summary of the nighttime sleep study with an N-AcetylMethyl GABA composition of this invention.

TABLE 10 Summary of Nighttime Study, 31 (Group 2) Human Patient OutcomesType of Change Quality/Symptom % Change Increase in Quality SleepQuality 84 Increase in Quality Restfulness/Wakefulness 86 Increase inQuality Mental Clarity/Memory 77 Increase in Quality Mood 104 Increasein Quality Daytime Energy 64 Reduction in Symptoms Stress 91 Reductionin Symptoms Anxiety 96 Reduction in Symptoms Body Aches/Pain 35Reduction in Symptoms Stress Headaches 100 Reduction in SymptomsDigestive Issues 25

Example 6 Daytime Study Study Purpose:

The Purpose of this study was to quantify the effectiveness of N-AcetylMethyl GABA on FAMMS (Fatigue, Anxiety, Mood, Mind, Stress) and relatedsymptoms and qualities. (Mind refers to mental clarity, memory andfocus).

GABA cannot cross the blood brain barrier. N-Acetyl Methyl GABA wascreated to provide a source of GABA that could cross the blood brainbarrier and act directly upon the CNS. Having a quantified study wasessential to demonstrating the effectiveness of N-Acetyl Methyl GABA.

Due to the above-described effects of N-Acetyl Methyl GABA on sleep andrelaxation, a sleep quality section was added to see how a “daytime”version of N-Acetyl Methyl GABA (administered without melatonin)assisted with sleep quality for daytime patients. This was alsobeneficial for patients that prefer not to take melatonin.

Study Design:

Study participants: 19 subjects

Duration:

7 day pre-study symptomology (no N-Acetyl Methyl GABA taken) to record abaseline of patient symptoms.

14 day study symptomology (taking N-Acetyl Methyl GABA) to recordpatient symptoms.

Criteria for Eligibility:

Age requirements: Anyone over the age of 12 was eligible to participatein the study.

Type of Patient:

Preferred subject would have minimum two of the following symptoms priorto study: FAMMS (Fatigue, Anxiety, Mood, Mind, Stress) (Mind definesmental clarity, memory and focus issues), sleep imbalance, insomnia,daytime energy issues.

Subjects were not asked to alter their normal life habits such asdrinking alcohol, smoking or caffeine.

Medications:

Subjects were asked to not use any additional mind/body stress relief ornatural supplements other than the N-Acetyl Methyl GABA composition(“GabaSorb® Daytime”) during the 14 day study.

Subjects were allowed to stay on any current medications they were on,if any, as long as they were noted.

All subjects reported that they did adhere to protocol.

Study Dosage:

Subjects were asked to take 2 teaspoons of the liquid N-Acetyl MethylGABA composition (Gabasorb Daytime) daily in the morning or earlyafternoon if they suffered from two or more symptoms listed in theprotocol.

Subjects were allowed to take the GabaSorb Daytime in the evening iftheir symptoms were more persistent during evening hours.

This also allowed for patients who wish not to take melatonin to takethe GabaSorb Daytime in the evening.

N-Acetyl Methyl GABA Composition:

The N-Acetyl Methyl GABA composition described in Table 11 was takenorally by each patient once daily.

TABLE 11 N-Acetyl Methyl GABA Composition % MGS-IU- COMPOSITION RM# TYPEINGREDIENT ML ACT % OV GMS-ML (W/W) 212 A DEIONIZED WATER 4970.0 1.00 04.9700 62.4%  209 A GLYCERINE USP 1181.0 1.00 0 1.1810 14.8%  3540 A MCTOIL 60/40 465.0 1.00 0 0.4650 5.8% 2707 A A-SOY LECITHIN LIQUID 400.01.00 0 0.4000 5.0% 3659 A N-ACETYL METHYL GABA 300.0 0.95 5 0.3316 3.8%2015 A ORANGE FLAVOR LIQ 186.0 1.00 0 0.1860 2.3% 1829 A XYLITOLGRANULAR (FINE) 150.0 1.00 0 0.1500 1.9% 3490 A SODIUM LAUROYL 56.0 1.000 0.0560 0.7% LACTYLATE 1348 A STEVIA EXT 90% 46.0 1.00 0 0.0460 0.6%2108 A BITTER MASK POWDER 30- 46.0 1.00 0 0.0460 0.6% 09 3635 A LUO HANGUO 50% 46.0 1.00 0 0.0460 0.6% 268 A PEPPERMINT OIL 33.0 1.00 0 0.03300.4% 2053 A GUAR GUM (COSMETIC 24.0 1.00 0 0.0240 0.3% GRADE) 384 ACINNAMON (CASSIA) OIL 24.0 1.00 0 0.0240 0.3% 255 A POTASSIUM SORBATE20.0 1.00 0 0.0200 0.25%  (GRAN) 298 A VITAMIN E OIL 18.0 1.00 0 0.01800.23%  DOSE WEIGHT = 7.965 GRAMS (approx. 8 g) 8 g 100% 

Study Dosage:

Subjects were administered 2 teaspoons (8 g) of the liquid N-AcetylMethyl GABA composition described above.

Table 12 shows patient outcomes for this study. Ratings were made eachday during the study period (7 days pre-administration, 14-days duringN-Acetyl Methyl GABA administration), based on a scale of 1 to 5.Improvements are shown by increased ratings over baseline in qualitiessuch as Stress, Anxiety, Mental Clarity and Memory, Mood, DaytimeEnergy, and Sleep Quality for each patient in Table 12. Patient genderand age for Table 12 are as follows: Patient 1 (P1): M/age 80, P2:F/47,P3:F/46; P4:F/31, P5:F/19, P6:F/62, P7:M/34, P8:F/47, P9:F/29, P10:M/59,P11:M/54, P12:M/38, P13:M/56, P14:M/22, P15:F/23, P16:M/50, P17:M/19,P18:F/44, P19:F27.

TABLE 12 Administration of N-Acetyl Methyl GABA in 19 human patients,daytime study without melatonin Mental Clarity/ Daytime Sleep StressAnxiety Memory Mood Energy Quality Reduced Reduced Improved ImprovedImproved Improved Patient # (%) (%) (%) (%) (%) (%) 1 48 35 57 20 40 782 45 32 55 94 32 95 3 36 22 72 39 88 118 4 33 40 43 68 88 150 5 72 46100 100 29 233 6 17 107 82 100 57 62 7 25 71 52 120 74 62 8 40 126 56152 36 77 9 78 57 131 88 42 93 10 69 56 70 129 23 57 11 27 63 59 100 1781 12 40 40 23 107 22 52 13 56 52 25 85 43 75 14 40 95 33 65 20 87 15 8589 71 100 11 78 16 41 63 16 60 0 79 17 52 56 30 69 22 52 18 55 63 33 11233 56 19 36 71 40 69 33 52

During the study, Patient 3 reported that during her use of the N-AcetylMethyl GABA composition, her menstrual cycle occurred, and she did notexperience cramping. She further advised she usually cramps heavilyduring her cycle and that this is the first time she did not experiencebad cramps. Patient 3 also reported less night sweats fromperimenopause.

During the study, Patient 18 reported that she is currently experiencingMenopause symptoms and that her symptoms seemed to be reduced. She alsoreported a reduction in mood swings and in irritability.

During the study, Patient 15 reported taking Lexapro® (escitalopram) foranxiety. She further reported that she felt like she could stop takingLexapro® with the N-Acetyl Methyl GABA composition, and that herpre-menstrual cycle (PMS) symptoms were reduced when taking the N-AcetylMethyl GABA composition (GabaSorb®).

Table 13 and FIG. 4 show a summary of patient outcomes in this studywith administration of an N-Acetyl Methyl GABA composition of thisinvention.

TABLE 13 Summary of Daytime Study, 19 Human Patient Outcomes Type ofChange Quality/Symptom % Change Reduction in Symptoms Stress 47Reduction in Symptoms Anxiety 62 Increase in Quality Mental Clarity and55 Memory Increase in Quality Mood 88 Increase in Quality Daytime Energy37 Increase in Quality Sleep Quality 86

Discussion

FIG. 3 summarizes improvements experienced by 47 subjects after 14 days'nighttime administration of an N-Acetyl Methyl GABA composition of thisinvention, including a daily dose of 300 mg N-Acetyl Methyl GABA and 5mg melatonin. As shown in FIG. 3 , overall the composition provided a92% reduction in stress and 110% reduction in anxiety in the subjects.Subjects further reported an 85% improvement in sleep quality, 86%improvement in restfulness/wakefulness, an 80% improvement in mentalclarity and memory, a 115% improvement in mood, and an 81% improvementin daytime energy, as well as a reduction in body aches and pains by45%, 135% reduction in stress headaches, and 32% reduction in digestiveissues, all after administration of an N-Acetyl Methyl GABA compositionfor 14 consecutive nighttime sleep periods.

FIG. 4 summarizes further studies showing improvements in 19 subjects'stress, anxiety, mental clarity and memory, mood, daytime energy, andsleep quality after administration of a 300 mg daily dose of an N-AcetylMethyl GABA composition, at a time of the subject's choosing and withoutmelatonin, for 14 consecutive days. As shown in FIG. 4 , overall thecomposition provided a 47% reduction in stress and 62% reduction inanxiety, as well as a 55% improvement in mental clarity and memory, 88%improvement in mood, 37% improvement in daytime energy, and 86%improvement in sleep quality.

The use of the terms “a,” “an,” “the,” and similar referents in thecontext of describing the present invention (especially in the contextof the claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. Recitation of ranges of values herein are merely intended toserve as a shorthand method of referring individually to each separatevalue falling within the range, unless otherwise indicated herein, andeach separate value is incorporated into the specification as if it wereindividually recited herein. Use of the term “about” is intended todescribe values either above or below the stated value in a range ofapproximately ±10%; in other embodiments, the values may range in valueabove or below the stated value in a range of approximately ±5%; inother embodiments, the values may range in value above or below thestated value in a range of approximately ±2%; in other embodiments, thevalues may range in value above or below the stated value in a range ofapproximately ±1%. The preceding ranges are intended to be made clear bycontext, and no further limitation is implied. All method stepsdescribed herein can be performed in any suitable order unless otherwiseindicated herein or otherwise clearly contradicted by context. The useof any and all examples, or exemplary language (e.g., “such as”)provided herein, is intended merely to better illuminate the inventionand does not pose a limitation on the scope of the invention unlessotherwise stated. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

While in the foregoing specification the present invention has beendescribed in relation to certain embodiments thereof, and many detailshave been put forth for the purposes of illustration, it will beapparent to those skilled in the art that the invention is susceptibleto additional embodiments and that certain of the details describedherein can be varied considerably without departing from the basicprinciples of the invention.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof, and,accordingly, reference should be made to the appended claims, ratherthan to the foregoing specification, as indicating the scope of theinvention.

1-11. (canceled)
 12. A method of aiding sleep and/or treating insomniain a subject comprising the steps of: a. providing a compositioncomprising N-Acetyl Methyl GABA and optionally melatonin; and b.administering the composition to the subject before a sleep period in anamount effective to increase the amount of N-Acetyl Methyl GABA in thesubject's bloodstream and brain tissue during the subject's sleep periodto aid sleep and/or treat insomnia; wherein said increased amount ofN-Acetyl Methyl GABA in the subject's bloodstream and tissue improvesthe subject's sleep quality during the subject's sleep period comparedwith sleep periods without the N-Acetyl Methyl GABA, and/or providesgood to excellent sleep quality during the sleep period.
 13. The methodof claim 12, wherein said effective amount is a daily dose of 200-600 mgN-Acetyl Methyl GABA.
 14. The method of claim 13, wherein said dose isabout 300 mg N-Acetyl Methyl GABA.
 15. The method of claim 12, whereinsaid administration occurs for at least 3 consecutive days.
 16. Themethod of claim 12, wherein said administration occurs less than 1 hourbefore the sleep period begins.
 17. The method of claim 12, wherein thesubject's mental clarity and memory, mood, daytime energy,restfulness/wakefulness, and/or sleep quality are improved after thesleep period.
 18. The method of claim 12, wherein body aches and pains,inflammation, irritability, stress headaches, and/or digestive issuesare decreased in the subject after the sleep period. 19-25. (canceled)26. The method of claim 12, said composition comprising about 1-10 mgmelatonin.
 27. The method of claim 12, said melatonin comprising about0.05% to about 0.1% w/w of the composition.
 28. The method of claim 15,wherein said administration occurs for 14 consecutive days.
 29. Themethod of claim 12, wherein in said administering step, said compositionis administered orally.
 30. The method of claim 12, said compositioncomprising: about 70% w/w deionized water, about 14.5% w/w glycerine,about 7.1% w/w soy lecithin liquid, about 3.8% w/w N-Acetyl Methyl GABA,about 1.3% w/w orange flavor liquid, about 1.0% w/w sodium lauroyllactylate, about 0.38% w/w stevia extract 90%, about 0.35% w/w bittermask powder, about 0.35% w/w Luo Han Guo 50%, about 0.31% w/w guar gum,about 0.28% w/w potassium sorbate (granular), about 0.25% w/w curcumin95%, about 0.22% w/w Vitamin E oil, about 0.125% w/w peppermint oil,about 0.125% w/w cinnamon (Cassia) oil, and about 0.06% w/w melatonin.31. The method of claim 30, wherein said N-Acetyl Methyl GABA is about300 mg.
 32. The method of claim 12, said composition comprising: about62.1% w/w deionized water, about 14.8% w/w glycerine, about 5.8% w/w MCToil 60/40, about 5.0% w/w soy lecithin liquid, about 3.8% w/w N-AcetylMethyl GABA, about 2.3% w/w orange flavor liquid, about 1.9% w/w xylitolgranular, about 0.7% w/w sodium lauroyl lactylate, about 0.6% w/w steviaextract 90%, about 0.6% w/w bitter mask powder, about 0.6% w/w Luo HanGuo 50%, about 0.4% w/w peppermint oil, about 0.3% w/w guar gum, about0.3% w/w cinnamon (Cassia) oil, about 0.25% w/w potassium sorbate(gran), about 0.23% w/w Vitamin E oil, and about 0.06% w/w melatonin.33. The method of claim 32, wherein said composition is in liquid formand said N-Acetyl Methyl GABA is about 300 mg.
 34. The method of claim12, said composition comprising: about 62.4% w/w deionized water, about14.8% w/w glycerine, about 5.8% w/w MCT oil 60/40, about 5.0% w/w soylecithin liquid, about 3.8% w/w N-Acetyl Methyl GABA, about 2.3% w/worange flavor liquid, about 1.9% w/w xylitol granular, about 0.7% w/wsodium lauroyl lactylate, about 0.6% w/w stevia extract 90%, about 0.6%w/w bitter mask powder, about 0.6% w/w Luo Han Guo 50%, about 0.4% w/wpeppermint oil, about 0.3% w/w guar gum, about 0.3% w/w cinnamon(Cassia) oil, about 0.25% w/w potassium sorbate, and about 0.23% w/wVitamin E oil.
 35. The method of claim 34, wherein said composition isin liquid form and said N-Acetyl Methyl GABA is about 300 mg.
 36. Themethod of claim 12, wherein said effective amount is a daily dose ofabout 10 mg to about 1000 mg N-Acetyl Methyl GABA.